UV-Resonance Raman Spectra of Systems in Complex Environments: A Multiscale Modeling Applied to Doxorubicin Intercalated into DNA

Abstract

UV-Resonance Raman (RR) spectroscopy is a valuable tool to study the binding of drugs to biomolecular receptors. The extraction of information at the molecular level from experimental RR spectra is made much easier and more complete thanks to the use of computational approaches, specifically tuned to deal with the complexity of the supramolecular system. In this paper, we propose a protocol to simulate RR spectra of complex systems at different levels of sophistication, by exploiting a quantum mechanics/molecular mechanics (QM/MM) approach. The approach is challenged to investigate RR spectra of a widely used chemotherapy drug, doxorubicin (DOX) intercalated into a DNA double strand. The computed results show good agreement with experimental data, thus confirming the reliability of the computational protocol.

Computational Insights into the Adsorption of Ligands on Gold Nanosurfaces

“…Clustering analysis for DOX in Figure S8 in Supporting Information shows that irrespectively of the FF, there are around five structural families, whose representative structures differ from each other in the flexibility of the anchor (substituent in the anthraquinone ring) and the daunosamine, the latter known to be involved in the groove binding when DOX is intercalated into DNA. This flexibility has already been reported in other works for free, solvated, and intercalated DOX. − As a matter of fact and unlike previous MD for DOX, ,, with the IFF/OPLS combination, one of the hydroxyl groups attached to the ring C (see Figure S8) rotates during the MD simulation, breaking the standard strong intramolecular interaction and being oriented toward the oxygen atom that bridges the sugar group, forming a new O–H···O HB.…”

“…This flexibility has already been reported in other works for free, solvated, and intercalated DOX. 88 − 91 As a matter of fact and unlike previous MD for DOX, 89 , 92 , 93 with the IFF/OPLS combination, one of the hydroxyl groups attached to the ring C (see Figure S8 ) rotates during the MD simulation, breaking the standard strong intramolecular interaction and being oriented toward the oxygen atom that bridges the sugar group, forming a new O–H···O HB.…”

The Resonance Raman Spectrum of Cytosine in Water: Analysis of the Effect of Specific Solute–Solvent Interactions and Non-Adiabatic Couplings

“…Consequently, vRR has been widely adopted to investigate the structural dynamics of photoexcited nucleobases [35,[40][41][42][43][44][45], nucleotides, [46], and oligonucleotides, [47,48], to cite some relevant papers. More recently, vRR has been used to characterize more complex DNA structures, and their interactions with therapeutic ligands [49][50][51][52][53].…”

Multiscale Frozen Density Embedding/Molecular Mechanics Approach for Simulating Magnetic Response Properties of Solvated Systems

“…QM/MM approaches generally treat the interaction between the two layers (classical and QM) at the purely electrostatic level; mutual polarization effects can indeed be included, giving rise to the so-called polarizable embedding methods, which yield a more physically consistent picture of the chemical system. ,− In most QM/classical methods, nonelectrostatic effects between the QM and classical portions, such as Pauli repulsion and dispersion, are neglected. However, these interactions can play an essential role in many systems, ranging from solutions , to biosystems. − Effective methods to introduce these interactions in QM/MM methods have been proposed, but their accuracy crucially relies on the appropriateness of parametrization . An alternative approach is to resort to quantum embedding methodologies, − which permit a correct description of Pauli repulsion by ensuring the orthogonality between the molecular orbitals of the two regions.…”

“…However, these interactions can play an essential role in many systems, ranging from solutions 13 , 14 to biosystems. 15 − 17 Effective methods to introduce these interactions in QM/MM methods have been proposed, but their accuracy crucially relies on the appropriateness of parametrization. 18 An alternative approach is to resort to quantum embedding methodologies, 19 − 40 which permit a correct description of Pauli repulsion by ensuring the orthogonality between the molecular orbitals of the two regions.…”